Astrocytes are the most abundant cell type in the central nervous system(CNS).They provide trophic support for neurons,modulate synaptic transmission and plasticity,and contribute to neuronal dysfunction.Many transgen...Astrocytes are the most abundant cell type in the central nervous system(CNS).They provide trophic support for neurons,modulate synaptic transmission and plasticity,and contribute to neuronal dysfunction.Many transgenic mouse lines have been generated to obtain astrocyte-specific expression of inducible Cre recombinase for functional studies;however,the expression patterns of inducible Cre recombinase in these lines have not been systematically characterized.We generated a new astrocyte-specific Aldh1 l1-CreER^(T2)knock-in mouse line and compared the expression pattern of Cre recombinase between this and five widely-used transgenic lines(hGfap-CreER^(T2)from The Jackson Laboratory and The Mutant Mouse Resource and Research Center,Glast-CreER^(T2),Cx30-CreER^(T2),and Fgfr3-iCreER^(T2))by crossing with Ai14 mice,which express tdTomato fluorescence following Cre-mediated recombination.In adult Aldh1 l1-CreER^(T2):Ai 14 transgenic mice,tdTomato was detected throughout the CNS,and five novel morphologicallydefined types of astrocyte were described.Among the six evaluated lines,the specificity of Cre-mediated recombination was highest when driven by Aldh1 l1 and lowest when driven by hGfap;in the latter mice,co-staining between tdTomato and NeuN was observed in the hippocampus and cortex.Notably,evident leakage was noted in Fgfr3-iCreER^(T2)mice,and the expression level of tdTomato was low in the thalamus when Cre recombinase expression was driven by Glast and in the capsular part of the central amygdaloid nucleus when driven by Cx30.Furthermore,tdTomato was clearly expressed in peripheral organs in four of the lines.Our results emphasize that the astrocyte-specific CreER^(T2)transgenic lines used in functional studies should be carefully selected.展开更多
Variability is one of the typical observational properties of blazars and the spectral changes are usually associated with variability,although this kind of association is unclear yet.In this work,we used data from th...Variability is one of the typical observational properties of blazars and the spectral changes are usually associated with variability,although this kind of association is unclear yet.In this work,we used data from the Steward Observatory blazar monitoring program to investigate the optical variability properties including the short-term timescale,the brightness-dependent spectral property,the correlation between the the brightness variation and the polarization,and then estimate the Doppler factors based on the obtained short timescale to study the polarization property for a sample of 20 TeV blazars.Our analyses arrive at the following results:(1)The largest variation amplitude in R-band,ΔR_(M),covers a range from ΔR_(M)=0.29 mag(1ES 2344+514)to ΔR_(M)=4.66 mag(3C 279).(2)Intra-day variability was found from five sources with timescales from 0.14 day for S50716+714 to 0.98 day for PKS 2155-304.Sixteen sources show spectra that are bluer when they become brighter,suggesting a common bluer-when-brighter property.(3)The plot of the polarization versus estimated Doppler factor is consistent with the Doppler factor dependent formula of polarization.(4)The largest polarization is correlated with the largest optical variation,suggesting that the high polarization and high amplitude variation are both the indicator of beaming effect.展开更多
Major depressive disorder(MDD) is a common mood disorder that affects almost 20% of the global population.In addition,much evidence has implicated altered function of the gamma-aminobutyric acid(GABAergic) system in t...Major depressive disorder(MDD) is a common mood disorder that affects almost 20% of the global population.In addition,much evidence has implicated altered function of the gamma-aminobutyric acid(GABAergic) system in the pathophysiology of depression.Recent research has indicated that GABA_B receptors(GABA_BRs) are an emerging therapeutic target in the treatment of stress-related disorders such as MDD.However,which cell types with GABA_BRs are involved in this process is unknown.As hippocampal dysfunction is implicated in MDD,we knocked down GABA_BRs in the hippocampus and found that knocking down these receptors in astrocytes,but not in GABAergic or pyramidal neurons,caused a decrease in immobility in the forced swimming test(FST) without affecting other anxiety-and depression-related behaviors.We also generated astrocytespecific GABABR-knockout mice and found decreased immobility in the FST in these mice.Furthermore,the conditional knockout of GABA_BRs in astrocytes selectively increased the levels of brain-derived neurotrophic factor protein in hippocampal astrocytes,which controlled the decrease in immobility in the FST.Taken together,our findings contribute to the current understanding of which cell types expressing GABA_BRs modulate antidepressant activity in the FST,and they may provide new insights into the pathological mechanisms and potential targets for the treatment of depression.展开更多
Every organism inevitably experiences stress. In the face of acute, intense stress, for example, periods of passivity occur when an organism's actions fail to overcome the challenge. The occurrence of inactive beh...Every organism inevitably experiences stress. In the face of acute, intense stress, for example, periods of passivity occur when an organism's actions fail to overcome the challenge. The occurrence of inactive behavior may indicate that struggling would most likely be fruitless.Repeated serious stress has been associated with mood disorders such as depression. The modulation of passive coping response patterns has been explored with a focus on the circuit level. However, the cellular and molecular mechanisms are largely uncharacterized. Here, we report that lactate is a key factor in the astrocytic modulation of the passive coping response to behavioral challenge in adult mice. We found increased extracellular lactate in the medial prefrontal cortex(mPFC) when mice experienced the forced swimming test(FST). Furthermore, we discovered that disturbing astrocytic glycogenolysis, which is a key step for lactate production in the mPFC, decreased the duration of immobility in the FST. Knocking down monocarboxylate transporter 4(MCT4), which is expressed exclusively in astrocytes and transports lactate from astrocytes to the extracellular space, caused similar results in the FST. The behavioral effect of both the pharmacological disturbance of astrocytic glycogenolysis and viral disruption of MCT4 expression was rescued via the administration of L-lactate. Moreover, we found that both pharmacological and viral modulation of astrocytederived lactate in mPFC slices increased the excitability of layer V pyramidal neurons, and this enhancement was reversed by exogenous L-lactate administration. These results highlight astrocyte-derived lactate as a biological mechanism underlying the passive coping response to behavioral challenge and may provide new strategies to prevent mood disorders.展开更多
Two different types of potential oscillations have been identified for the first time during dichromate reduction on a gold electrode in a solution of dilute sulfuric acid. One occurs before hydrogen evolution due to ...Two different types of potential oscillations have been identified for the first time during dichromate reduction on a gold electrode in a solution of dilute sulfuric acid. One occurs before hydrogen evolution due to the formation and dissolution of passivating films of low-valence chromium oxides, and the other generates, accompanying periodic hydrogen evolution, from the coupling of electrochemical reactions with diffusive and convective mass transport. More interestingly, these two types of oscillations correspond to two crossing loops in the cyclic voltammogram （CV）. Such a relation of oscillations with crossed CVs will provide a new way to find electrochemical oscillatory systems systematically and rapidly.展开更多
基金supported by Grants from the National Natural Science Foundation of China(31430032,31830033,81971080,and 81671356)the Program for Changjiang Scholars and Innovative Research Teams in University(IRT_16R37)+1 种基金the Science and Technology Program of Guangdong(20188030334001)the Guangzhou Science and Technology Project(201707020027,201704020116)。
文摘Astrocytes are the most abundant cell type in the central nervous system(CNS).They provide trophic support for neurons,modulate synaptic transmission and plasticity,and contribute to neuronal dysfunction.Many transgenic mouse lines have been generated to obtain astrocyte-specific expression of inducible Cre recombinase for functional studies;however,the expression patterns of inducible Cre recombinase in these lines have not been systematically characterized.We generated a new astrocyte-specific Aldh1 l1-CreER^(T2)knock-in mouse line and compared the expression pattern of Cre recombinase between this and five widely-used transgenic lines(hGfap-CreER^(T2)from The Jackson Laboratory and The Mutant Mouse Resource and Research Center,Glast-CreER^(T2),Cx30-CreER^(T2),and Fgfr3-iCreER^(T2))by crossing with Ai14 mice,which express tdTomato fluorescence following Cre-mediated recombination.In adult Aldh1 l1-CreER^(T2):Ai 14 transgenic mice,tdTomato was detected throughout the CNS,and five novel morphologicallydefined types of astrocyte were described.Among the six evaluated lines,the specificity of Cre-mediated recombination was highest when driven by Aldh1 l1 and lowest when driven by hGfap;in the latter mice,co-staining between tdTomato and NeuN was observed in the hippocampus and cortex.Notably,evident leakage was noted in Fgfr3-iCreER^(T2)mice,and the expression level of tdTomato was low in the thalamus when Cre recombinase expression was driven by Glast and in the capsular part of the central amygdaloid nucleus when driven by Cx30.Furthermore,tdTomato was clearly expressed in peripheral organs in four of the lines.Our results emphasize that the astrocyte-specific CreER^(T2)transgenic lines used in functional studies should be carefully selected.
基金supported by the National Natural Science Foundation of China(NSFC,grant Nos.U2031201,12433004,11733001,U2031112,12133004,and 12103012)Guangdong Major Project of Basic and Applied Basic Research(grant No.2019B030302001)+1 种基金the science research grants from the China Manned Space Project with NO.CMS-CSST-2021-A06supported by the Key Laboratory for Astronomical Observation and Technology of Guangzhou。
文摘Variability is one of the typical observational properties of blazars and the spectral changes are usually associated with variability,although this kind of association is unclear yet.In this work,we used data from the Steward Observatory blazar monitoring program to investigate the optical variability properties including the short-term timescale,the brightness-dependent spectral property,the correlation between the the brightness variation and the polarization,and then estimate the Doppler factors based on the obtained short timescale to study the polarization property for a sample of 20 TeV blazars.Our analyses arrive at the following results:(1)The largest variation amplitude in R-band,ΔR_(M),covers a range from ΔR_(M)=0.29 mag(1ES 2344+514)to ΔR_(M)=4.66 mag(3C 279).(2)Intra-day variability was found from five sources with timescales from 0.14 day for S50716+714 to 0.98 day for PKS 2155-304.Sixteen sources show spectra that are bluer when they become brighter,suggesting a common bluer-when-brighter property.(3)The plot of the polarization versus estimated Doppler factor is consistent with the Doppler factor dependent formula of polarization.(4)The largest polarization is correlated with the largest optical variation,suggesting that the high polarization and high amplitude variation are both the indicator of beaming effect.
基金supported by grants from the National Natural Science Foundation of China (31430032,31830033, 81671356,and 31600864)the Program for Changjiang Scholars and Innovative Research Teams in University (IRT_16R37)+2 种基金the Science and Technology Program of Guangdong Province,China (2018B030334001)the Guangzhou Municipal Science and Technology Project (201707020027)the Postdoctoral Science Foundation of China (2018M633072)。
文摘Major depressive disorder(MDD) is a common mood disorder that affects almost 20% of the global population.In addition,much evidence has implicated altered function of the gamma-aminobutyric acid(GABAergic) system in the pathophysiology of depression.Recent research has indicated that GABA_B receptors(GABA_BRs) are an emerging therapeutic target in the treatment of stress-related disorders such as MDD.However,which cell types with GABA_BRs are involved in this process is unknown.As hippocampal dysfunction is implicated in MDD,we knocked down GABA_BRs in the hippocampus and found that knocking down these receptors in astrocytes,but not in GABAergic or pyramidal neurons,caused a decrease in immobility in the forced swimming test(FST) without affecting other anxiety-and depression-related behaviors.We also generated astrocytespecific GABABR-knockout mice and found decreased immobility in the FST in these mice.Furthermore,the conditional knockout of GABA_BRs in astrocytes selectively increased the levels of brain-derived neurotrophic factor protein in hippocampal astrocytes,which controlled the decrease in immobility in the FST.Taken together,our findings contribute to the current understanding of which cell types expressing GABA_BRs modulate antidepressant activity in the FST,and they may provide new insights into the pathological mechanisms and potential targets for the treatment of depression.
基金supported by grants from the National Natural Science Foundation of China(31830033,81671356,81971080)the Program for Changjiang Scholars and Innovative Research Team in University(IRT_16R37)Key-Area Research and Development Program of Guangdong Province(2018B030334001)。
文摘Every organism inevitably experiences stress. In the face of acute, intense stress, for example, periods of passivity occur when an organism's actions fail to overcome the challenge. The occurrence of inactive behavior may indicate that struggling would most likely be fruitless.Repeated serious stress has been associated with mood disorders such as depression. The modulation of passive coping response patterns has been explored with a focus on the circuit level. However, the cellular and molecular mechanisms are largely uncharacterized. Here, we report that lactate is a key factor in the astrocytic modulation of the passive coping response to behavioral challenge in adult mice. We found increased extracellular lactate in the medial prefrontal cortex(mPFC) when mice experienced the forced swimming test(FST). Furthermore, we discovered that disturbing astrocytic glycogenolysis, which is a key step for lactate production in the mPFC, decreased the duration of immobility in the FST. Knocking down monocarboxylate transporter 4(MCT4), which is expressed exclusively in astrocytes and transports lactate from astrocytes to the extracellular space, caused similar results in the FST. The behavioral effect of both the pharmacological disturbance of astrocytic glycogenolysis and viral disruption of MCT4 expression was rescued via the administration of L-lactate. Moreover, we found that both pharmacological and viral modulation of astrocytederived lactate in mPFC slices increased the excitability of layer V pyramidal neurons, and this enhancement was reversed by exogenous L-lactate administration. These results highlight astrocyte-derived lactate as a biological mechanism underlying the passive coping response to behavioral challenge and may provide new strategies to prevent mood disorders.
文摘Two different types of potential oscillations have been identified for the first time during dichromate reduction on a gold electrode in a solution of dilute sulfuric acid. One occurs before hydrogen evolution due to the formation and dissolution of passivating films of low-valence chromium oxides, and the other generates, accompanying periodic hydrogen evolution, from the coupling of electrochemical reactions with diffusive and convective mass transport. More interestingly, these two types of oscillations correspond to two crossing loops in the cyclic voltammogram （CV）. Such a relation of oscillations with crossed CVs will provide a new way to find electrochemical oscillatory systems systematically and rapidly.
